Abstract: TH-PO345
The Striking Finding of Multiciliated Proximal Tubular Cells in Patients with Tubular Injury
Session Information
- AKI: Repair and Regeneration
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Acute Kidney Injury
- 002 AKI: Repair and Regeneration
Authors
- Eymael, Jennifer, Radboudumc, Nijmegen, Netherlands
- Willemsen, Brigith, Radboudumc, Nijmegen, Netherlands
- Mooren, Fieke, Radboudumc, Nijmegen, Netherlands
- Wetzels, Jack F., Radboudumc, Nijmegen, Netherlands
- Dijkman, Henry, Radboudumc, Nijmegen, Netherlands
- Van der vlag, Johan, Radboudumc, Nijmegen, Netherlands
- Smeets, Bart, Radboudumc, Nijmegen, Netherlands
Background
Cilia are evolutionary highly conserved antennae-like structures with important functions in cell signaling and homeostasis. In kidney epithelial cells, one primary cilium per cell can be detected, which serves as flow sensor and consists of 9 peripheral microtubular doublets. Motile cilia can be found on multiciliated cells and additionally express a central microtubule pair, dynein arms and radial spoke proteins (e.g. RSPH4A) required for ciliary motion. Motile cilia assembly involves activation of the transcription factors FOXJ1 and RFX3. In this study, the unexpected detection of multiciliated cells in patients with tubular injury was evaluated.
Methods
Immunofluorescent staining was performed on patient biopsies with markers for cilia, specific tubular segments and for motile cilia (RSPH4A). In addition the expression of FOXJ1 and RFX3 was studied. The ciliary ultrastructure was analyzed by transmission electron microscopy.
Results
Multiciliated cells were initially detected in five patients. All patients were affected by tubular injury with different underlying pathologies. Multiciliated cells were localized in the proximal tubule. Furthermore, cilia on multiciliated cells stained positive for RSPH4A and the motile cilia structure (9+2) was detected by transmission electron microscopy. Co-expression of FOXJ1 and RFX3 in multiciliated cells was observed, indicating activation of motile cilia assembly. Analysis of additional biopsies from 20 patients with severe tubular injury revealed the presence of multiciliated cells in 4 cases (20%).
Conclusion
Multiciliated proximal tubular cells with motile cilia were frequently observed in patients with tubular injury. The mechanism underlying this phenomenon and the possible function of multiciliated cells in the kidney, need further investigation.
A) Immunofluorescence showing multicilia (green, arrow) and FOXJ1 expression (purple).
B) TEM showing a multiciliated proximal tubule cell with motile cilia (9+2 structure).
Funding
- Private Foundation Support